Chun-Hua Chang1, Ting-Tsz Ou1, Mon-Yuan Yang1, Chi-Chou Huang2, Chau-Jong Wang3. 1. Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan. 2. School of Medicine, Chung Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan; Department of Surgery, Division of Colon and Rectum, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, Taiwan. 3. Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, Taiwan. Electronic address: wcj@csmu.edu.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood. THE AIM OF THIS STUDY: The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells. RESULTS: We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function. CONCLUSION: The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer.
ETHNOPHARMACOLOGICAL RELEVANCE: Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood. THE AIM OF THIS STUDY: The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells. RESULTS: We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function. CONCLUSION: The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer.
Authors: Jie Li; Xia Gong; Rong Jiang; Dan Lin; Tao Zhou; Aijie Zhang; Hongzhong Li; Xiang Zhang; Jingyuan Wan; Ge Kuang; Hongyuan Li Journal: Front Pharmacol Date: 2018-07-31 Impact factor: 5.810